The world leader in serving science
Gibco Bulk Process Liquid and Buffer Capabilities
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• $17 billion in revenues
• $700 million spent on R&D
• 50,000 employees
• 50 countries
• 5 premier brands
The World Leader in Serving Science
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Cell Culture and Cell Therapy History
1962 1970 1980 1990 2000 2010 2012 2014
Growing with you at every stage for over 50 years
Grand Island
Biologics
Company
founded in 1962
First manufacturing facility opens in
Grand Island, NY in 1965
Gibco and BRL combine
to form Life
Technologies in 1983
Gibco™ AIM V™ Medium launched in 1987 (first product to be used for patient treatment)
Gibco™ CD CHO
Medium launched in
1996 (first chemically
defined complete media)
Invitrogen acquires Life
Technologies in 2000
Gicbo™ Advanced
Granulation
Technology™ (AGT™)
format in 2001
Animal
origin–free
facility in
2005
ISO
13485
in 2007
Invitrogen acquires
Applied
Biosystems in
2008
Optima
Autofiller in
2009
Gibco celebrates 50 years
Distribution
expansion in
2012
2016
Bulk liquid manufacturing in
Grand Island
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Leading Capabilities for Every Step of the Bioprocess Workflow
Upstream Downstream
Cell line development and
media optimization
Mixing, cell culture
and fermentation
Harvest and
collection Purification
Bulk storage and
final fill
Microbial identification Glycan analytics
Mycoplasma and viral detection
Automation solutions for nucleic acid sample preparation
Analytical columns
QC and analysis
CHO cell lines
Process development
services
Media optimization
services
Cell culture media, feeds
and enhancers
Single-use fermentors,
bioreactors and mixers
BioProcess Containers
(BPCs)
Integrity testing solutions
Harvest and separation
products
Storage and transport
Single-use frozen
handling system
Single-use sampling
system
Chromatography resins
Affinity ligands and resins
Transfer assemblies
Host cell DNA, host cell
protein and protein A
quantitation
Storage and transport
Single-use fermentors,
bioreactors and mixers
Single-use BPCs, manifolds
and containers
Single-use frozen
handling system
QC and analytics
Single-use heat exchanger
Large-volume liquids
Large-volume liquids
Single-use mixers
Single-use filling system
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Global BioProduction Manufacturing Facilities
Logan, Utah
• BioProcess Containers
• Single-use technologies
• Class 10,000/ISO 7
clean room
Matamoros, Mexico
• BioProcess Containers
• Single-use technologies
• ISO 13485
• cGMP standards
Millersburg, PA • BioProcess Containers
• Single-use technologies
• ISO 13485
• cGMP standards
Bedford and
Framingham, MA
• Chromatography resins
• ISO 13485
Grand Island, NY
• Cell culture media, reagents
• Sera
• ISO 13485
• GMP 21 CFR 820
Cramlington, UK
• Bioprocess containers
• Single-use technologies
• Class 10,000/ISO 7
clean room
Warrington, UK
• Analytics kits
Naarden, the Netherlands
• Affinity ligands
• ISO 9001–certified
Paisley, Scotland
• Cell culture media,
reagents
• ISO 13485
• GMP 21 CFR 820
Auckland and
Christchurch, New Zealand;
Newcastle, Australia
• Sera
• Protein products
• GMP 21 CFR 820
Lillestrom and Oslo,
Norway
• Invitrogen™ Dynabeads™
Magnetic Beads
• ISO 9001– and
ISO 13485–certified
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Gibco Media Network
Serving over 110 commercial therapies worldwide
US manufacturing Grand Island, New York
EMEA manufacturing Paisley, Scotland
Dry powder
media
AGT
media
1X
media/buffer
Concentrated
media/buffers
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Reliably Serving Customers with Operational Excellence
• Redundant manufacturing facilities
• Persistent facility and capability investment
• Supply chain and supplier development
• Multilevel safety stock management
• Continuous investment in business continuity planning
• Robust, defined, and proven quality management systems
• Dedicated animal origin–free manufacturing capabilities
• Highly specific analytical methods to reduce risk of contamination
• Testing of raw materials and in-process/finished goods
• Fully integrated serum sourcing and manufacturing in country of origin
• Documented and controlled manufacturing procedures
• Process validation and statistical process control (SPC)
• High-functioning process and continuous improvement (PPI)
• Formalized system of customer interactions and priorities
Assurance
of supply
Quality
Process
control and
improvement
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Benefits to Outsourcing Bioprocess Liquid Manufacturing
• Better product consistency
• Improved cell culture performance
• Suppliers of liquids are more knowledgeable and experienced
• Fewer contamination risks
• Eliminate need for mixing tanks
• Time and labor-intensive steps eliminated:
• QC of salts, liquid preparation, filtration, quarantine, finished good
testing, documentation, procedures, validation
• Improved safety due to less handling
• Just-in-time logistics solutions
• Doe & Ingalls cGMP warehousing (in US)
Advantages Customer benefit
Increased productivity
Improved quality and compliance
Decreased capital and operating costs
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Multiple Film Offerings for BPCs
Proven history
• Extensive liquid handling experience
• Over 20 years’ experience customizing single-use assemblies
• Over 1 million BPCs produced yearly
Custom products optimized
• For the application
• For specific operating parameters
• Using qualified components
• To meet time and cost requirements
Film choices for liquids
• BPCs with Thermo Scientific™ CX5-14 and Aegis™ films are
validated for liquid fills and shipments from Grand Island and Paisley
• Thermo Scientific™ ASI™ 26/77 film qualification for fill and shipment
(Grand Island and Paisley) initiated in 2016
• Continuing to support legacy films Final assembly
BPC film Chamber inspection
ASI film (Millersburg, PA)
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Critical Attributes Help Ensure Product Integrity and Performance
Characteristics that determine whether a flexible container will maintain product integrity and perform as
expected during specific bioprocess operations
• Biological compatibility
• Tensile properties
• Puncture resistance
• Glass transition temperature
• Transportability
• Clarity
• Permeability
• pH stability
• Extractable profile
• Cell culture growth performance
• Stability
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Expanded Choice of Secondary Packaging
5, 10, and 20 L
bioprocess containers
50, 100, and 200 L
bioprocess containers
100, 200, 500, and 1,000 L
bioprocess containers
• Corrugate cases
• Returnable plastic crates
• Option to ship in different drum designs
• Top-emptying
• Bottom-emptying
• Nestable
• Single-trip
• Hazardous material handling
• ALLpaQ (Arca/Auer) plastic
returnable systems
• Bottom- or top-emptying
• 100 and 200 L returnable
containers only available in EU
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Mitigate risk
• Quality compliance and raw
material traceability
• On-time delivery and backorder
management
• Change notice and corrective
action management
Increase productivity
• Dedicated account
management team
• Raw material handling services
• Supplier management
• Document management
Reduce costs
• cGMP chemical storage
• Inventory solutions
• Increased lots and consolidated
shipments
Doe & Ingalls*—Chemical Production and Distribution
Extension of your supply chain management and finished goods distribution
* Available only in the US.
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Aspiration: Best-in-Class Bulk Liquid Manufacturing
Bulk process liquids and buffers increase biopharmaceutical process efficiency and reduce risk by simplifying
and standardizing workflows
Why?
• Outsource partnership/manufacturing
extension
• Pronounced synergies with vertical integration
• Existing liquid and single-use
technologies expertise
• Enables cost reduction for customers
What?
• Manufacturing capacity
• Cold warehouse space and distribution
• Support resources
• Process optimization
2014 2015 2016
• Launch integrated custom large-volume
liquid (LVL) portfolio
• Grand Island expansion project scope
• Liquid facility investments (US & EU)
• Water for injection (WFI) launch (20 & 200 L)
• Facility / equipment implementation
• Validation
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Liquid Production Network
Grand Island, USA Paisley, Scotland
Bottled liquids (10 mL–1 L)
Bagged liquids (1–1,000 L)
Batch sizes (10–10,000 L)
Corrosive solutions (5,000 L polypropylene tank)
Alcohols (up to 20% v/v ethanol) (750–2,500 L)
Formulation Filtration Dispensing Fill and finish Order management Delivery
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Bulk liquid
addition
Warehouse
addition
Grand Island Liquid Facility Investments
Grand Island facility expansion for bulk liquids Q4 2016
Facility footprint
• 15,000 ft2 manufacturing over two floors
• 12,400 ft2 finished goods warehouse space
• Clean room, gowning, storage,
formulation, staging
Equipment deployed
• Multiple 10,000 liter tanks
• 5,000 liter tank
• 2,500 liter tank
Support systems
• WFI still
• HVAC
• Clean steam generation
• Electronic batch records
$21.8M investment to
increase liquid
manufacturing
(5 million liters)
Additional capabilities
added to include an
alcohol suite to manage
hazardous solutions
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Design Criteria and Quality Standards
Design criteria Value Rank
ISO 13485 Internationally recognized standard on the requirements for a quality management system for medical devices Industry standard
21 CFR 820–compliant FDA current Good Manufacturing Practice (cGMP) quality system regulation for medical devices Industry standard
Annex 1 standard cGMP guidelines to harmonize US/EU controls and procedures to manufacture sterile medicinal products Differentiator
Animal origin–free (AOF) All raw materials are free of animal-derived components; dedicated AOF equipment Differentiator
Grade C and grade D
controlled spaces Monitored and controlled temperature, pressure, air change rate for formulation and filtration Differentiator
Single material flow One-way raw material flow with no return to inventory; dedicated AO/AOF raw materials for manufacturing Differentiator
Proximity to raw material and
finished goods warehouse Segregated AO/AOF raw material sampling booths; close proximity to manufacturing and distribution Differentiator
2nd floor formulation Gravity transfer to fill and filtration for ergonomic workflow; separate formulation suites for each tank Differentiator
Manifold filling Semiautomated closed manifold system Differentiator
To meet current and future customer requirements for insourcing bulk liquids,
our Grand Island manufacturing facility is built to and compliant with the
following standards:
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Lister
building
Fleming
building MacLeod
building
LSG EMEA headquarters 600 employees In Scotland since 1970
Kelvin
building
Incremental Investments to Improve Liquid Capacity in Europe
New
10,000 L
tank
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Liquid Capacity Exceeds Demand
Robust systems to accommodate increased demand
Number of tanks 400–1,000 L 1,500–2,500 L 3,000–10,000 L
Grand Island 2 5 6
Paisley 3 2 4
Ways to increase
capacity
• 24x7
• Additional headcount
• Bolt-on tankage
• Use disposables
Capacity
assumptions
Capacity
variables
• 5x3 shift operation
• Existing people
• Tank utilization <75%
• Tanks
• Workflow (24x6, 24x7)
• Number of people 7.4M liters
8.3M liters
14.4M liters
0
2
4
6
8
10
12
14
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2014 2015 2016
Mil
lio
n lit
ers
Grand Island Paisley Demand
• Additional
FTE
• New WFI
system
• New
10,000 L
tank
New bulk
facility in
Grand Island
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Examples of Customer Liquid Projects
Liquid type Gibco™ product and annual volume examples
Cell culture media
GMEM: [66,000 L] 330 x 200 L bag
Custom media formulation: [462,500 L] 925 x 500 L bag
AIM V T cell Medium: 15,000 x 1 L bag
Feeds and additives
10% antifoam: [13,000 L] 2,600 x 5 L bag
CHO CD EfficientFeed™ A supplement: [3,800 L] 760 x 5 L bag
BME: 8,130 x 1 L bottle
Bioprocess liquids
Sodium citrate: [90,000 L] 450 x 200 L bag
PBS: [32,000 L] 1,600 x 20 L bag
WFI: [28,000 L] 2,800 x 10 L bag
Concentrates CD CHO concentrate: [296, 400 L] 1,800 x 150 L bag + 1,320 x 20 L bag
1,000X CD lipids: [3,900 L] 1,950 x 2 L bottle
Total liquid volume in 2015
• 8.3M liters of catalog and custom
liquids
• 2.0M liters in bioprocess containers
• 6.3M liters in bottles
Gibco BioProduction services
• Media / buffer / concentrate
development
• Process development
• Scale-up / technology transfer
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Outsourced Buffers Provide Cost and Time Savings
Batch size 2,000 L 10,000 L
Batches per year 20 4
QC releases 20 4
Prep time (2,000 L) 4 hours 1 hour
Annual prep time 10 days 2.5 days
0.1 M NaOH buffer cost analysis
In-house
75% reduction in prep time
80% reduction in lot testing
Total batch cost $11,500 $35,000
Per liter cost $5.75 $3.50
Annual prep time $230,000 $140,000
$90,000 annual savings
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More Choice and Control Through Manufacturing Flexibility
Liquid format
• Process liquids for upstream and
downstream applications
• Gibco media and feeds for cell
culture processes
• 1X and concentrates
Container type
• Bottles from 10 mL–1 L
• Flexible bioprocess containers
from 1–1,000 L
• Custom designs and sizing
available
Film choice
• Industry-standard CX5-14 film for
general applications
• Aegis5-14 film for critical
applications
• Industry-standard ASI 26/77 film
for general applications
Manufacturing speed
• Non-GMP Gibco™ Media
Express™ (GME) services
• Full GMP for scale-up
The right liquid format, container, and manufacturing process for each product
Streamlined management of order, manufacturing, testing, storage, and delivery
Order
acknowledgement Manufacturing
Quotation
provided QC testing
Feasibility
assessment
COA and
shipping
Learn more at thermofisher.com/bioprocessliquids
The world leader in serving science
Results matter.
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